The broad aim of this 5 year research study is to advance the understanding of the biological basis of schizotypal personality disorder (SPD), using neuropsychological, electrophysiological, and magnetic resonance imaging (MRl) studies on DSM III-R-diagnosed schizotypal patients and age-, sex-, and parental socioeconomic status-matched normal controls. In comparison to schizophrenia, many of the biological aspects of SPD have not been intensively studied, despite the intrinsic interest of SPD and the fact that it is a part of the "schizophrenia spectrum" of disorders. Genetic-epidemiologic studies now suggest that the spectrum disorders share a common heritability, and thus raise the prospect that studying SPD subjects would allow studies of the biological substrate and markers of spectrum disorders without the complicating and perhaps confounding factors present when schizophrenic subjects are studied -- chronic illness, chronic medication, and chronic hospitalization. Accordingly, we propose to apply the approach and technology we have found fruitful in schizophrenia studies to SPD. A pilot study has produced striking findings suggesting that SPD patients do indeed have many of the biological characteristics of schizophrenics, including disorders of verbal memory (deficient clustering on the California Verbal Learning test) and a trend to Wisconsin Card Sorting Test Abnormalities, abnormalities of the P300 event-related potential (ERP), which indexes processing of unusual stimuli, and MRI volume reduction of gray matter of amygdala/hippocampus and increase in CSF in the temporal, horn of the lateral ventricles, with both anomalies especially prominent on the left. We plan to study 50 SPD and 50 normal control subjects, all right-handed and all without any history of neuroleptic medication and no current psychotropic medication. Clinical measures include the Chapman schizotypy scales, SANS and SAPS, and the thought disorder index. The Beck Depression inventory and the State-Trait Anxiety scale will be used to measure any potential confounds from depression or anxiety. On MRI, we predict automated segmentation of fast spin echo 2 mm slices will show no overall abnormalities of CSF spaces or of gray and white matter volumes. However, we predict that manually defined ROI from 1.5x1x1 mm SPGR data will show left-lateralized volume reductions in medial temporal lobe (amygdala/hippocampus and parahippocampal gyrus), in superior temporal gyrus, and in prefrontal cortex. A neuropsychological test battery will seek to determine more precisely the nature of the CVLT and WCST abnormalities, which we predict will be replicated in a larger subject group, and will correlate with temporal and prefrontal abnormalities. We predict a replication of our preliminary P300 findings of overall amplitude reduction and of a left < right temporal region asymmetry, correlated with MRI volume reduction of the left superior temporal gyrus. We predict an automatic P300a amplitude decrease correlated with prefrontal cortex volume. We further predict reduction in amplitude of the N400 ERP, associated with processing of incongruent linguistic stimuli, and for this to be correlated with medial temporal lobe and superior temporal gyrus volume reductions. Overall we predict a pattern of functional and structural pathology to emerge that is compatible with a disturbance in temporal lobe and prefrontal cortex, and to their joint systems. Comparison of SPD and schizophrenic pathology will help us begin to determine whether they differ mainly in intensity of functional and structural pathology or whether schizophrenia, the most severe spectrum disorder, has distinctive features, thereby implicating environmental and/or non-spectrum heritable factors in its causation.